Prodrugs are defined as precursors to therapeutic agents that release the active ingredient under the action of metabolic processes. Usually, prodrugs are useful when the active agent has pharmacological insufficiencies, whether on formulation or in delivery. Prodrug activation may occur due to enzymatic and/or non-enzymatic processes in vivo. Prodrug design is particularly applicable when modifying the overall hydrophobic/hydrophilic character of the drug for enhancing absorption into the body.
Hydromorphone is a commonly used analgesic and antitussive agent that is typically delivered orally because the molecule is quite polar. Because of the increasing use of hydromorphone to treat chronic pain, there is a need for transdermal and other delivery systems of this compound. Accordingly, there is a need for hydrophobic derivatives of hydromorphone. Ideally, these hydrophobic derivatives would be in the form of prodrugs that would be converted into active hydromorphone upon transdermal or transmucosal transport.